The differentiation of the nervous system depends on a sequence of related developmental decisions. These decisions - mediated by cell-cell interactions - include (1) the choice between neural versus non-neural cellular lineages, (2) the subsequent choice among the wide variety of specific neural cell fates, and (3) the choice of appropriate target cells with which to synapse. The long-term goal of this project is to understand the molecular basis of each of these important developmental decisions. In Project 1, led by Chris Kintner, we will study the role of a pair of interacting receptor-ligand proteins (Notch and Delta) in neural specification in the developing Xenopus embryo. In functional studies, we will test the hypothesis that, as in Drosophila, these two molecules play a determinative role in the initial choice of neural versus non- neural cell fate. In Project 2, led by Greg Lemke, we will study the structure and function of four new neural receptor tyrosines kinases (Tyrol 2, 3, and 6). Proteins related to the Tyros are known to function as receptors for neurotrophic regulators such as Nerve Growth Factor, and to directly control the choice between specific neural cell fates. In project 3, led by John Thomas, we have capitalized on the genetics of Drosophila to identify a gene (bendless) that controls the final choice of synaptic targets in a well-defined neuronal circuit. We will identify the bendless gene product and study its role in the target recognition process. These experiments will provide us with fundamental insights into the cellular interactions that mediate neural development, and a detailed understanding of their molecular basis.